BACKGROUND. Protein and amino acids are
among the most common nutritional supplements taken by athletes. This
review evaluates the theoretical rationale and potential effects on
athletic performance of protein, purported anabolic amino acids,
branched-chain amino acids, glutamine, creatine, and hydroxymethylbutyrate (HMB).
LITERATURE.
Two books, 61 research articles, 10 published abstracts, and 19 review
articles or book chapters. FINDINGS. Dietary supplementation of
protein beyond that necessary to maintain nitrogen balance does not provide
additional benefits for athletes. Ingesting carbohydrate with protein prior
to or following exercise may reduce catabolism, promote glycogen
resynthesis, or promote a more anabolic hormonal environment. Whether employing
these strategies during training enhances performance is not yet clear.
There is some evidence from clinical studies that certain amino acids
(e.g., arginine, histidine, lysine, methionine, ornithine, and
phenylalanine) have anabolic effects by stimulating the release of growth
hormone, insulin, and/or glucocorticoids, but there is little evidence that
supplementation of these amino acids enhances athletic performance.
Branched-chain amino acids (leucine, isoleucine, and valine) and glutamine
may be involved in exercise-induced central fatigue and immune suppression,
but their ergogenic value as supplements is equivocal at present. Most
studies indicate that creatine supplementation may be an effective and safe
way to enhance performance of intermittent high-intensity exercise and to
enhance adaptations to training. Supplementation with hydroxymethylbutyrate
appears to reduce catabolism and increase gains in strength and fat-free
mass in untrained individuals initiating training; as yet, limited data are
available to decide how it affects training adaptations in athletes. CONCLUSIONS. Of the nutrients reviewed,
creatine appears to have the greatest ergogenic potential for athletes
involved in intense training. FURTHER RESEARCH. All supplements reviewed here
need more evaluation for safety and effects on athletic performance. Reprint · Reference List · Help

Amino acids are the building blocks of protein in the body; assuch they
are essential for the synthesis of structural proteins,enzymes, and some
hormones and neurotransmitters. Amino acids arealso involved in numerous
metabolic pathways that affect exercisemetabolism. Consequently, it has been
suggested that athletesinvolved in intense training require additional
protein in the dietor that they should supplement their diet with specific
amino acids.I review here the rationale and the evidence for the
potentialergogenic effect of short-term supplementation with protein and
aminoacids and the evidence for the potential anabolic effect oflonger-term
use when supplementation is combined with training. Ideal first with protein,
then with the amino acids under thefollowing headings: the potentially
anabolic amino acids; thebranched-chain amino acids, which have a somewhat
different role inmetabolism and in their potential effect on performance;
glutamine,which is in a class of its own for its effects on the immune
system;creatine, an amino acid that is not one of the building blocks
ofprotein but is involved in short-term energy production in muscle;and
hydroxymethylbutyrate (HMB), a potentially anabolic metabolite ofthe amino
acid leucine.

LITERATURE

This review is an update rather than an exhaustive account of allpublished
works on the topic. I have cited two books, 60 researcharticles, 10 published
abstracts, and 18 review articles/bookchapters from my own database of
references. In my database there area further 97 research articles, 78
abstracts, and 38 reviewarticles/book chapters on the topic. These additional
references arereviewed elsewhere (Kreider, 1999; Kreider,1998; Williams et al.,
1999). Downloadthe complete list as a Word 97 file by clicking on thislink.

FINDINGS
ProteinA considerable amount of research has evaluated dietaryprotein
needs of athletes. Although there is some debate, moststudies indicate that
in order to maintain protein balance duringintense resistance and/or
endurance training, athletes should ingestapproximately 1.3 to 1.8 g protein
per kg body mass per day(Butterfield, 1991; Lemon,1998; Kreider et al., 1993;
Kreider,1999). Athletes training at high-altitude
may need as much as 2.2g protein per kg per day in order to maintain protein
balance(Butterfield, 1991). This protein
intakeis about 1.5 to 2 times the recommended dietary allowance (RDA) forthe
normal adult. In most instances an iso-energetic diet can providethe required
protein, but athletes who maintain hypo-energetic diets,do not ingest enough
quality protein in their diet, and/or train ataltitude may be susceptible to
protein malnutrition (Kreider,1999). In theory, this
state could slow tissue growth and/orrecovery from training. On the other
hand, ingesting more proteinthan necessary to maintain protein balance during
training (e.g.,> 1.8 g/kg/d) does not promote greater gains in strength
orfat-free mass (Lemon et al., 1992;Tarnopolsky et al., 1992). Thesefindings
indicate that athletes typically do not need to supplementtheir normal diets
with protein, provided they ingest enough qualityprotein to maintain protein
balance.

Researchers have expended a considerable amount of effort onevaluating the
effects of supplementation of branched-chain aminoacids (BCAAs: leucine,
isoleucine, and valine) on physiological andpsychological responses to
exercise (Blomstrandet al., 1991; Kreider, 1998; Wagenmakers,1998).
There are two primary hypotheses regarding the ergogenicvalue of
supplementation with these amino acids.

First, BCAA supplementation has been reported to decreaseexercise-induced
protein degradation and/or muscle enzyme release (anindicator of muscle
damage) possibly by promoting an anti-catabolichormonal profile (Carli et al., 1992;Coombes and
McNaughton, 1995).Theoretically, BCAA supplementation during intense
training may helpminimize protein degradation and thereby lead to greater
gains infat-free mass. Although several studies support this
hypothesis,additional research is necessary to determine the long-term
effectsof BCAA supplementation during training on markers of catabolism,body
composition, and strength (Kreider,1998).

Second, the availability of BCAA during exercise has beentheorized to
contribute to central fatigue (Newsholmeet al., 1991).
During endurance exercise, BCAAs are taken up bythe muscles rather than the
liver in order to contribute to oxidativemetabolism. The source of BCAAs for
muscular oxidative metabolismduring exercise is the plasma BCAA pool, which
is replenished throughthe catabolism of whole body proteins during endurance
exercise(Davis, 1995; Kreider,1998;
Newsholme et al., 1991).However, the oxidation of
BCAAs in the muscle during prolongedexercise may exceed the catabolic
capacity to increase BCAAavailability, so plasma BCAA concentration may
decline duringprolonged endurance exercise (Blomstrand
etal., 1988; Blomstrand et al., 1991).The
decline in plasma BCAAs during endurance exercise can result inan increase in
the ratio of free tryptophan to BCAAs. Free tryptophanand BCAAs compete for
entry into the brain via the same amino-acidcarrier (Newsholme
et al., 1991).Therefore, a decrease in BCAAs in the blood facilitates
entry oftryptophan into the brain. Moreover, most tryptophan in the blood
isbound to albumin, and the proportion of tryptophan bound to albuminis
influenced by the availability of long-chained fatty acids(Davis
et al., 1992; Newsholmeet al., 1991). In
endurance exercise free fatty-acidconcentration rises, so the amount of
tryptophan bound to albuminfalls, increasing the concentration of free
tryptophan in the blood(Davis, 1995).

Collectively, the decline in plasma BCAAs and increase in freetryptophan
during prolonged endurance exercise alters the ratio offree tryptophan to
BCAAs and increases the entry of tryptophan intothe brain (Newsholme et al., 1991). Anincreased concentration of
tryptophan in the brain promotes theformation of the neurotransmitter
5-hydroxytryptamine (5-HT). 5-HThas been shown to induce sleep, depress motor
neuron excitability,influence autonomic and endocrine function, and suppress
appetite inanimal and human studies. An exercise-induced imbalance in the
ratioof free tryptophan to BCAAs has been implicated as a possible causeof
acute physiological and psychological fatigue (central fatigue).It has also
been hypothesized that chronic elevations in 5-HTconcentration, which may
occur in athletes maintaining high-volumetraining, explains some of the
reported signs and symptoms of theovertraining syndrome: postural
hypotension, anemia, amenorrhea,immunosuppression, appetite suppression,
weight loss, depression, anddecreased performance (Newsholme
et al.,1991; Gastmann and Lehmann, 1998;Kreider, 1998).

A number of studies have recently been conducted to evaluatewhether
carbohydrate and/or BCAA supplementation affects centralfatigue during
exercise and/or signs and symptoms of overtraining.Analysis of this
literature indicates that carbohydrate and/or BCAAsupplementation during
exercise can affect the ratio of freetryptophan to BCAA. For example,
carbohydrate administration duringexercise has been reported to attenuate FFA
release and minimizeincreases in the free tryptophan:BCAA ratio (Daviset al., 1992). In addition, BCAA supplementation has
beenreported to increase plasma BCAA concentration and minimize and/orprevent
increases in the ratio of free tryptophan to BCAAs (Blomstrandet
al., 1991). Studies also indicate that BCAA administrationwith or without
carbohydrate prior to and during exercise can affectphysiological and
psychological responses to exercise (Coombesand
McNaughton, 1995; Hefler et al.,1993; Kreider et al., 1992; Kreiderand
Jackson, 1994).

Nevertheless, the effect of these nutritionally-inducedalterations in the
free tryptophan to BCAA ratio on physicalperformance is still not clear. Most
studies indicate that BCAAsupplementation does not improve single-bout
endurance performance,but these studies almost certainly lacked power to
delimit small butuseful enhancements of performance (Davis,1995;
Gastmann and Lehmann, 1998;Kreider,
1998). Additional research is alsonecessary to determine the effect of
long-term BCAA supplementationon training adaptations and the signs and
symptoms of overtraining(Kreider, 1998).

Preliminary studies indicate that supplementation withbranched-chain amino
acids (4 to 16 g) and/or glutamine (4 to 12 g)can prevent the decline or even
increase glutamine concentrationduring exercise (Kreider,
1998). In theorythese changes in glutamine concentration could have
beneficialeffects on protein synthesis and immune function. However, in the
fewstudies of increased glutamine availability, there was little or noeffect
on performance or immune status (Rohde etal., 1998; Nieman and Pedersen, 1999). Itis also unclear whether
long-term supplementation of glutamineaffects protein synthesis, body
composition, or the incidence ofupper respiratory-tract infections during
training.

Creatine

Creatine is a naturally occurring amino acid derived from theamino acids
glycine, arginine, and methionine (Balsomet al., 1994;
Williams et al., 1999).Most creatine is stored in
skeletal muscle, primarily asphosphocreatine; the rest is found in the heart,
brain, and testes(Balsom et al., 1994; Kreider,1998). The daily requirement of creatine is
approximately 2 to 3g; half is obtained from the diet, primarily from meat
and fish,while the remainder is synthesized (Williams
etal., 1999). Creatine supplementation has been proposed as a meansto
"load" muscle with creatine and phosphocreatine (PCr). In theory,an
increased store of creatine or phosphocreatine would improve theability to
produce energy during high intensity exercise as well asimprove the speed of
recovery from high-intensity exercise.

Ingesting
carbohydrate/protein prior to exercise may reduce catabolism whereas
ingesting carbohydrate/protein following exercise may promote glycogen
resynthesis, a more anabolic hormonal environment, and recovery. The
extent to which these strategies affect training adaptations is unknown.

There is some
evidence from clinical populations that certain amino acids (e.g.,
arginine, histidine, lysine, methionine, ornithine, and phenylalanine)
may stimulate the release of growth hormone, insulin, and/or
glucocorticoids and thereby promote anabolic processes. However, there
is little evidence that supplementation of these amino acids provides
ergogenic benefit for athletes.

Branched-chain amino
acids and glutamine have been hypothesized to affect central fatigue and
exercise-induced immune suppression, but their ergogenic value during
prolonged exercise is equivocal at present.

Most studies
indicate that creatine supplementation may be an effective and safe
means to enhance intermittent high-intensity exercise performance as
well as training adaptations. Of the nutrients evaluated, creatine
appears to have the greatest ergogenic potential for athletes involved
in intense training.

Hydroxymethylbutyrate
supplementation has been reported to reduce catabolism and promote
greater gains in strength and fat-free mass in untrained individuals
initiating training. Limited data are available on the effects of HMB
supplementation on training adaptations in athletes.

FURTHERRESEARCH

Over the last few decades researchers have found that amino acidsplay
multiple roles in metabolism. For this reason, researchers andathletes are
interested in the effects of amino-acid supplementationon exercise metabolism,
exercise performance, and trainingadaptations. Although significant advances
have been made, muchremains to be learned about these effects. Researchers
should alsoevaluate the long-term safety of amino-acid supplementation, as
wellas the potential medical value in the treatment of variousdiseases.